Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy.

Female Reproductive Health Disturbance Experienced During the COVID-19 Pandemic Correlates With Mental Health Disturbance and Sleep Quality.

The COVID-19 pandemic has adversely affected population mental health. Periods of psychological distress can induce menstrual dysfunction. We previously demonstrated a significant disruption in women's reproductive health during the first 6 months of the pandemic.

The Impact of the COVID-19 Pandemic on Women's Reproductive Health.

Background: The COVID-19 pandemic has profoundly affected the lives of the global population. It is known that periods of stress and psychological distress can affect women's menstrual cycles. We therefore performed an observational study of women's reproductive health over the course of the pandemic thus far.

Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study.

Background: Adrenal insufficiency (AI) is associated with increased cardiovascular morbidity and mortality and reduced quality of life (QoL). Optimum glucocorticoid (GC) dosing and timing are crucial in the treatment of AI, yet the natural circadian secretion of cortisol is difficult to mimic. The once-daily dual-release hydrocortisone (DR-HC) preparation (Plenadren®), offers a more physiological cortisol profile and may address unmet needs.

The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy.

Background: Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group.

Outcomes of the short Synacthen test: what is the role of the 60 min sample in clinical practice?

Unlabelled: In recent years, the short Synacthen test (SS) has become the most widely used test to assess adrenal reserve. Despite its frequent use, there are still several areas related to the short Synacthen test (SST), which have no consensus including the optimum sampling times, that is, whether a 60 min post-Synacthen administration cortisol is necessary or not.

Methodology: We performed a retrospective data analysis of 492 SSTs performed on adult patients in a tertiary referral teaching hospital in Ireland.

EED and EZH2 constitutive variants: A study to expand the Cohen-Gibson syndrome phenotype and contrast it with Weaver syndrome.

Overgrowth-intellectual disability (OGID) syndromes are characterized by increased growth (height and/or head circumference ≥+2 SD) in association with an intellectual disability. Constitutive EED variants have previously been reported in five individuals with an OGID syndrome, eponymously designated Cohen-Gibson syndrome and resembling Weaver syndrome. Here, we report three additional individuals with constitutive EED variants, identified through exome sequencing of an OGID patient series.

Rates of abnormal aldosterone/renin ratio in African-origin compared to European-origin patients: A retrospective study.

Introduction: The aldosterone/renin ratio is the initial screening test for primary hyperaldosteronism (PHA), but little data exists regarding ethnic variations in this.

Methods: Following clinical observation of a high prevalence of abnormal aldosterone/renin ratio (ARR) in patients of African-origin, we retrospectively reviewed all ARR measurements in a single centre over 10 years. Rates of hypokalaemia, intraventricular septal thickness (IVS, by echocardiography) and adrenal imaging were recorded when available.

DIFFERENTIAL REGULATION OF 11β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 ACTIVITY IN PATIENTS WITH DIFFERING ETIOLOGIES OF HYPOPITUITARISM.

Objective: Pituitary patients with different etiologies of hypopituitarism exhibit differing phenotypes, despite similar replacement therapy strategies. We hypothesized that differential regulation of the isoenzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which mediates the net autocrine conversion of cortisone to cortisol in adipose tissues and liver, may play a role.

Methods: We studied 11β-HSD1 activity (using urine cortisol/cortisone metabolites ratio) in 36 hypopituitary patients with treated craniopharyngiomas, treated remitted Cushing disease, and treated nonfunctioning pituitary adenomas + prolactinomas on and off growth hormone (GH) replacement.

In women with PCOS, waist circumference is a better surrogate of glucose and lipid metabolism than disease status per se.

Objective: Cardiometabolic abnormalities are recognized in polycystic ovary syndrome (PCOS). However, over-emphasis on PCOS as a risk factor potentially results in over-investigation and treatment of some women with and under-recognition of cardiometabolic risk in obese women without PCOS. Our objective was to explore the association between waist circumference (WC) and indices of glucose and lipid metabolism in women with and without PCOS.

Towards a personalized approach to aromatase inhibitor therapy: a digital microfluidic platform for rapid analysis of estradiol in core-needle-biopsies.

Despite advances in breast cancer prevention and treatment, variability in patient-response has revealed the need for a more "personalized" approach to medicine, in which treatments are tailored to each patient's biology. Motivated by this idea, we introduce a technique that allows for quantification of small-molecule analytes directly from core needle biopsy (CNB) tissue samples on a miniaturized platform. The new technique, powered by digital microfluidics, integrates tissue-liquid extraction and magnetic bead-based competitive immunoassay for quantification of estradiol in milligram-sized CNB samples.

Immediate versus modified release hydrocortisone in mitotane-treated patients with adrenocortical cancer.

Objective: Mitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane-treated ACC patients yet.

Low-dose hydrocortisone replacement is associated with improved arterial stiffness index and blood pressure dynamics in severely adrenocorticotrophin-deficient hypopituitary male patients.

Objective: Increased cardiovascular and cerebrovascular morbidity and mortality in hypopituitary subjects may be linked to inappropriate glucocorticoid exposure; however, the pathophysiology remains unclear. We aimed to examine the effect of three commonly prescribed hydrocortisone (HC) regimens on vascular risk factors.

Design: An open crossover study randomising ten hypopituitary men with severe adrenocorticotrophic hormone deficiency to three HC dose regimens: dose A (20mg mane and 10mg tarde), dose B (10mg mane and 10mg tarde) and dose C (10mg mane and 5mg tarde).

Short-term sleep deprivation with nocturnal light exposure alters time-dependent glucagon-like peptide-1 and insulin secretion in male volunteers.

The intestinal L cell is the principal source of glucagon-like peptide-1 (GLP-1), a major determinant of insulin release. Because GLP-1 secretion is regulated in a circadian manner in rodents, we investigated whether the activity of the human L cell is also time sensitive. Rhythmic fluctuations in the mRNA levels of canonical clock genes were found in the human NCI-H716 L cell model, which also showed a time-dependent pattern in their response to well-established secretagogues.

Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders--an observational pilot study.

Objective: To investigate whether temporarily withholding FSH and adding androgen could improve follicular response during a microdose flare protocol in women with slow follicular growth or asynchronous follicular development.

Design: Observational pilot study.

Setting: University-affiliated private fertility center.

The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure.

Context: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy.

Objective: To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.

Symptoms of gonadal dysfunction are more predictive of hypopituitarism than nonspecific symptoms in screening for pituitary dysfunction following moderate or severe traumatic brain injury.

Objective: The economic and logistic burden of screening for hypopituitarism following moderate/severe traumatic brain injury (TBI) is considerable. A key recommendation in published guidelines is to prioritize for screening those patients with symptoms suggestive of pituitary dysfunction. The purpose of this study was to evaluate the utility of targeted screening for hypopituitarism in long-term survivors after moderate/severe TBI using referrals on the basis of symptoms.

A microfluidic technique for quantification of steroids in core needle biopsies.

Core needle biopsy (CNB) sampling is known to be inexpensive and minimally invasive relative to traditional tissue resectioning. But CNBs are often not used in analytical settings because of the tiny amount of sample and analyte. To address this challenge, we introduce an analytical method capable of multiplexed steroid quantification in CNB samples-those studied here ranged in mass from 2 to 8 mg.

Aromatase inhibitors for prevention of breast cancer in postmenopausal women: a narrative review.

Objective: The increasing incidence of breast cancer (BC) worldwide has resulted in widespread interest in primary prevention therapies. A number of large randomized trials have shown that selective estrogen receptor modulators can reduce the relative risk for BC by 30% to 40% in high-risk women. In early-stage BC, aromatase inhibitors (AIs) showed a 35% relative reduction in the risk of contralateral BCs compared with tamoxifen.

A novel compound heterozygous mutation of the luteinizing hormone receptor -implications for fertility.

The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) belongs to the family of G-protein coupled receptors and binds both luteinizing hormone (LH) and human chorionic gonadotropin (hCG). Ligand-receptor interaction mediates a downstream cascade of events which is essential for ovulation in women, and expression of the male phenotype in men. The human LHCGR gene consists of 11exons and 10 introns.

Low-dose hydrocortisone replacement therapy is associated with improved bone remodelling balance in hypopituitary male patients.

Objective: Glucocorticoid (GC) therapy is associated with adverse effects on bone metabolism, yet the effects of different GC physiological replacement regimens in hypopituitarism are not well characterised. We aimed to assess the effect of three hydrocortisone (HC) replacement dose regimens on bone turnover.

Study Design: An open cross-over study randomising ten hypopituitary men with severe acth deficiency to three commonly used HC dose regimens: dose A (20 mg mane and 10 mg tarde), dose B (10 mg mane and 10 mg tarde) and dose C (10 mg mane and 5 mg tarde).

Association between Sleep Disruption and Levels of Lipids in Caucasians with Type 2 Diabetes.

Aim. To investigate the association between sleep quality and duration with lipid and glycaemic control in Caucasian subjects with type 2 diabetes. Methods.

Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.

Background: The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15-30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens.

Objective: Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL).

The interaction between growth hormone and the thyroid axis in hypopituitary patients.

Alterations in the hypothalamo-pituitary-thyroid axis have been reported following growth hormone (GH) administration in both adults and children with and without growth hormone deficiency. Reductions in serum free thyroxine (T4), increased tri-iodothyronine (T3) with or without a reduction in serum thyroid-stimulating hormone secretion have been reported following GH replacement, but there are wide inconsistencies in the literature about these perturbations. The clinical significance of these changes in thyroid function remains uncertain.

The natural history of surgically treated but radiotherapy-naïve nonfunctioning pituitary adenomas.

Background And Objectives: Transsphenoidal surgery is indicated for patients with nonfunctioning pituitary adenomas (NFPAs) causing compressive symptoms. Previous studies attempting to define the rate of recurrence/regrowth of surgically treated but radiation-naïve NFPAs were somewhat limited by selection bias and/or small numbers and/or lack of consistency of findings between studies. A better understanding of the natural history of this condition could allow stratification of recurrence risk and inform future management.